Study Links Estrogen, Depression

The combination of estrogen and stress may make women more susceptible to anxiety and depression than men, a study by researchers at the Yale University School of Medicine suggests.

The study was one of the first that attempted to find a molecular reason why women are about twice as likely to experience major depression and anxiety disorders as men, said Rebecca Shansky, a graduate student in Yale's neurobiology department and lead author of the study, which will appear in the March issue of the journal Molecular Psychiatry.

Stress has been implicated in the development of major depression, a condition that is marked by disruption in an area of the brain called the prefontal cortex. The prefrontal cortex regulates behavior, thought and working memory -- the ability to plan and organize behavior.

Shansky and other Yale neurobiologists decided to place rats under stress to gauge the influence estrogen levels have on the rats' ability to complete simple memory tasks.

Without any stress, male rats and female rats performed memory tasks equally well. And with high levels of stress, male and female rats both made a lot of errors. However, male rats performed significantly better at memory tasks than females when placed under moderate stress.

On closer study, researchers discovered that female rats performed poorly on the tests only during proesterus, when they produced high levels of estrogen. During estrus, or with low estrogen levels, there was no impairment.

The scientists then removed the ovaries of female rats and repeated the experiment, giving some rats estrogen replacement and others placebos. Again, they found that female rats with high levels of estrogen performed worse on memory tasks than those without.

The results suggest that estrogen may amplify the negative effect of stress on the brain's ability to complete certain tasks, Shansky said. It could be that estrogen also increases susceptibility to stress-related disorders, such as depression and anxiety, and why the increased risk ends at menopause, she said.

Dr. Nicholas DeMartinis, assistant professor of psychiatry at the University of Connecticut Health Center, said estrogen can have some beneficial effects on the serotonin system, which often malfunctions in depressed patients. DeMartinis speculated that in some women, the combination of high levels of stress and estrogen interferes with serotonin regulation and triggers depression, he said.

Teasing out female-specific contributing factors may have great value in developing new treatments for anxiety and depression, DeMartinis said.